The present invention relates to new compounds having an element of group 12 and having a tridentate ligand, a process for their preparation and their use in particular as polymerization catalysts.
The use of derivatives having an element of group 12 but having porphyrin type ligands (Inoue, Acc. Chem. Res., (1996) 29, 39) as catalysts for the polymerization of heterocycles is already known.
However, it has been shown that each type of catalyst used for the polymerizations or copolymerizations, produces different polymers or copolymers respectively (Jedlinski et al., Macromolecules, (1990) 191, 2287; Munson et al., Macromolecules, (1996) 29, 8844; Montaudo et al., Macromolecules, (1996) 29, 6461). The problem is therefore to find new catalytic systems in order to obtain new polymers or copolymers, and more particularly block copolymers. The use of catalytic systems allows control of the chain formation of monomers leading to specific copolymers having the appropriate properties. This is particularly useful for biocompatible copolymers, the biodegradation of which is influenced by this chain formation.
Therefore a subject of the invention is the products of general formula I 
in which
M represents an element of group 12;
RM represents the hydrogen atom, a halogen atom, or an alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, alkylthio, cycloalkylthio, arylthio, amino, alkylamino, dialkylamino, cycloalkylamino, di(cycloalkyl)amino, alkyl(cycloalkyl)amino, arylamino, diarylamino, alkylarylamino or (cycloalkyl)arylamino radical;
A and B represent, independently, a carbon chain of 2 to 4 carbon atoms, optionally substituted by one or more of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl or aryl radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical;
L1 and L2 represent, independently, a group of formula -E15(R15)xe2x80x94 in which
E15 is an element of group 15 and
R15 represents the hydrogen atom; one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl or aryl radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; a radical of formula -E14RRxe2x80x2Rxe2x80x3 in which E14 is an element of group 14 and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, alkylthio, cycloalkylthio or arylthio radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; or a radical of formula xe2x80x94SO2Q in which Q represents a halogen atom, an alkyl, haloalkyl or aryl radical optionally substituted by one or more substituents chosen from the alkyl, haloalkyl and halogen radicals.
L3 indifferently represents a group of formula -Exe2x80x215(Rxe2x80x215)(Rxe2x80x315) or -E16(R16) in which
Exe2x80x215 is an element of group 15 and
E16 is an element of group 16 and
Rxe2x80x215, Rxe2x80x315 and R16 represent, independently, the hydrogen atom; one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl or aryl radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; a radical of formula -Exe2x80x214 TTTxe2x80x3 in which Exe2x80x214 is an element of group 14 and T, Txe2x80x2 and Txe2x80x3 represent, independently, the hydrogen atom or one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, alkylthio, cycloalkylthio or arylthio radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; or a radical of formula xe2x80x94SO2Qxe2x80x2 in which Qxe2x80x2 represents a halogen atom, an alkyl, haloalkyl or aryl radical optionally substituted by one or more substituents chosen from the alkyl, haloalkyl and halogen radicals.
In the definitions indicated above, the expression halogen represents a fluorine, chlorine, bromine or iodine atom, preferably chlorine. The expression alkyl preferably represents a linear or branched alkyl radical having 1 to 6 carbon atoms and in particular an alkyl radical having 1 to 4 carbon atoms such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl radicals.
The term haloalkyl preferably designates radicals in which the alkyl radical is as defined above and is substituted by one or more halogen atoms as defined above such as, for example, bromoethyl, trifluoromethyl, trifluoroethyl or also pentafluoroethyl. The alkoxy radicals can correspond to radicals in which the alkyl radical is as defined above. The methoxy, ethoxy, isopropyloxy or tert-butyloxy radicals are preferred. The alkylthio radicals preferably represent radicals in which the alkyl radical is as defined above such as, for example, methylthio or ethylthio. The alkylamino and dialkylamino radicals preferably represent the radicals in which the alkyl radical is as defined above such as, for example, methylamino or dimethylamino.
The cycloalkyl radicals are chosen from saturated or unsaturated monocyclic cycloalkyls. The saturated monocyclic cycloalkyl radicals can be chosen from the radicals having 3 to 7 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl radicals. The unsaturated cycloalkyl radicals can be chosen from cyclobutene, cyclopentene, cyclohexene, cyclopentadiene and cyclohexadiene radicals. The cycloalkoxy radicals can correspond to radicals in which the cycloalkyl radical is as defined above. The cyclopropyloxy, cyclopentyloxy or cyclohexyloxy radicals are preferred. The cycloalkylthio radicals can correspond to radicals in which the cycloalkyl radical is as defined above such as for example cyclohexylthio. The cycloalkylamino and di(cycloalkyl)amino radicals can correspond to radicals in which the cycloalkyl radical is as defined above such as for example cyclohexylamino and di(cyclohexyl)amino.
The aryl radicals can be of mono or polycyclic type. The monocyclic aryl radicals can be chosen from the phenyl radicals optionally substituted by one or more alkyl radicals, such as tolyl, xylyl, mesityl and cumenyl. The polycyclic aryl radicals can be chosen from the naphthyl, anthryl and phenanthryl radicals. The aryloxy radicals can correspond to radicals in which the aryl radical is as defined above. The phenoxy, 2,4,6-tritertiobutylphenoxy, tolyloxy or mesityloxy radicals are preferred. The arylthio radicals preferably designate the radicals in which the aryl radical is as defined above such as for example in phenylthio radicals. The arylamino and diarylamino radicals preferably designate radicals in which the aryl radical is as defined above such as, for example, phenylarnino or diphenylamino radicals.
The alkyl (cycloalkyl)amino radicals can correspond to radicals in which the alkyl and cycloalkyl radicals are as defined above such as, for example methyl(cyclohexyl)amino.
The alkyl arylamino radicals preferably designate radicals in which the alkyl and aryl radicals are as defined above such as, for example methylphenylamino. The (cycloalkyl)arylamino radicals can correspond to the radicals in which the cycloalkyl and aryl radicals are as defined above such as, for example (cyclohexyl)phenylamino.
The compounds of formula 1 can be presented in the form of a monomer or of a dimer and more particularly the compounds of formula 1 in which M represents a zinc atom generally presented in dimer form.
A more particular subject of the invention is the products of general formula I as defined above, characterized in that
RM represents an alkyl radical;
A and B represent, independently, a carbon chain with 2 to 4 carbon atoms;
L1 and L2 represent, independently, a radical of formula -E15(R15)xe2x80x94 in which E15 is a nitrogen or phosphorus atom and R15, represents a hydrogen atom or a radical of formula -E14RRxe2x80x2Rxe2x80x3 in which E14 represents a carbon or silicon atom and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or an alkyl radical;
L3 represents a radical of formula -Exe2x80x215(Rxe2x80x215)(Rxe2x80x315) in which Exe2x80x215 is a nitrogen or phosphorus atom, and Rxe2x80x215 and Rxe2x80x315 represent, independently, a hydrogen atom or a radical of formula -Exe2x80x214TTxe2x80x2Txe2x80x3 in which Exe2x80x214 represents a carbon or silicon atom and T, Txe2x80x2 and Txe2x80x3 represent, independently, the hydrogen atom or an alkyl radical.
Preferably, M represents a zinc atom. Preferably also, RM represents a methyl radical; A and B represent, independently, a carbon chain with 2 carbon atoms; L1 and L2 represent, independently, a radical of formula -E15(R15)xe2x80x94 in which E15 is a nitrogen atom and R15 represents a hydrogen atom, a methyl, ethyl, propyl, isopropyl radical or a radical of formula -E14RRxe2x80x2Rxe2x80x3 in which E14 represents a silicon atom and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or a methyl, ethyl, propyl or isopropyl radical; L3 represents a radical of formula -Exe2x80x25(Rxe2x80x215)(Rxe2x80x315) in which Exe2x80x215 is a nitrogen atom, and Rxe2x80x215 and Rxe2x80x315 represent, independently, a hydrogen atom, a methyl, ethyl, propyl, isopropyl radical or a radical of formula -Exe2x80x214TTxe2x80x2Txe2x80x3 in which Exe2x80x214 represents a silicon atom and T, Txe2x80x2 and Txe2x80x3 represent, independently, the hydrogen atom or a methyl, ethyl, propyl or isopropyl radical.
More particularly, a subject of the invention is the products described hereafter in the examples, in particular the products corresponding to the following formulae:
- [Me3SiN(H)CH2CH2N(Me)CH2CH2NSiMe3]ZnMe;
- [Me3SiN(H)CH2CH2N(H)CH2CH2NSiMe3]ZnMe.
A subject of the invention is also a process for the preparation of the. products of general formula I as defined above, characterized in that a product of formula 1
xe2x80x83(L1-A-L2-B-L3)xe2x88x92, Y+xe2x80x83xe2x80x83(I)
in which L1, A, L2, B and L3 have the meanings indicated above and Y represents the hydrogen atom, a metal or a metallic group, is reacted with a product of formula II
MRMZxe2x80x83xe2x80x83(II)
in which M and RM have the meanings indicated above and Z represents a parting group, in order to obtain a product of formula I as defined above.
The reaction of a compound of general formula I with a compound of general formula II in order to obtain a compound of general formula 1, can be carried out under an inert atmosphere such as under a freon or argon atmosphere, in an aprotic solvent, at a temperature comprised between xe2x88x9290 and +50xc2x0 C. The compounds I thus obtained are purified by standard purification methods.
As aprotic solvent, aromatic hydrocarbons such as benzene, toluene; aliphatic hydrocarbons such as pentane, heptane, hexane, cyclohexane; ethers such as diethylether, dioxane, tetrahydrofuran, ethyltertiobutyl ether can be used.
In the Compounds I, Y represents the hydrogen atom, a metal or a metallic group. The metallic group can be a compound of formula Rxe2x80x2xe2x80x3M1 or Rxe2x80x2xe2x80x33M2 in which Rxe2x80x2xe2x80x3 represents a halogen atom, or indifferently, an alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy or aryloxy radical as previously defined, M1 is a zinc or mercury atom or an alkaline-earth such as magnesium and M2 a tin or lead atom; preferably, the metallic group is chosen from the MgBr, ZnMe, SnMe3, SnBu3 or PbMe3 groups. The metal can be an alkali metal chosen from lithium, sodium or potassium.
In the compounds II, Z represents a parting group such as a halogen atom, an alkyl, cycloalkyl, alkoxy, aryl, aryloxy, amino, alkylamino or dialkylamino group as previously defined, or also a methanesulphonyloxy, a benzenesulphonyloxy, p-toluenesulphonyloxy group.
The starting products of formula I are known products or can be prepared from known products. For their synthesis, the following references can be mentioned: Cloke et al., J. Chem. Soc., Dalton Trans. (1995) 25; Wilkinson and Stone, Comprehensive Organometallic Chemistry (1982) vol. 1, 557.
The products of formula II are commercially available or can be manufactured by methods known to a person skilled in the art.
A subject of the invention is also the use of the products of formula 1 as defined above, as catalysts for carrying out (co)polymerization, that is to say of polymerization or copolymerization. Whilst carrying out (co)polymerization, the compounds according to the invention also play the role of chain initiator and/or of regulator.
The compounds of formula 1 are particularly useful for carrying out the polymerization of heterocycles. The heterocycles can contain one or more heteroatoms of groups 15 and/or 16, and have a size ranging from three to eight members. As an example of heterocycles corresponding to the previous formulation, epoxides, thioepoxides, cyclic esters or thioesters such as lactones, lactames and anhydrides can be mentioned.
The compounds of formula I are also particularly useful for carrying out the (co)polymerization of cyclic esters. As an example of cyclic esters, the polymer cyclic esters of lactic and/or glycolic acid can be mentioned. Random or block copolymers can be obtained depending on whether the monomers are introduced together at the start of the reaction, or sequentially during the course of the reaction.
A subject of the invention is also a process for the preparation of random or block copolymers, or polymers which consists of bringing into contact one or more monomers, a chain initiator and/or a regulator, a polymerization catalyst and optionally a polymerization solvent, said process characterized in that the chain initiator and/or chain regulator and the polymerization catalyst are represented by the same compound which is chosen from the compounds of formula (I) as defined above.
The (co)polymerization can be carried out either in solution or in supercooling. When the (co)polymerization is carried out in solution, the reaction solvent can be the (or one of the) substrate(s) used in the catalytic reaction. Solvents which do not interfere with the catalytic reaction itself, are also suitable. As an example of such solvents, saturated or aromatic hydrocarbons, ethers, aliphatic or aromatic halides can be mentioned.
The reactions are carried out at temperatures comprised between ambient temperature and approximately 250xc2x0 C.; the temperature range comprised between 40 and 200xc2x0 C. is most advantageous. The durations of the reactions are comprised between a few minutes and 300 hours, and preferably between 5 minutes and 72 hours.
This (co)polymerization process is particularly suitable for obtaining (co)polymers of cyclic esters, in particular the polymer cyclic esters of lactic and/or glycolic acid. The products obtained such as the biodegradable glycolic lactic copolymers, are advantageously used as a support in sustained release therapeutic compositions. The process is also particularly well suited to the polymerization of epoxides, in particular propylene oxide.
The polymers obtained are compounds which can be used for the synthesis of organic liquid crystals or also as semi-permeable membranes.
The invention also relates to the polymers or copolymers which can be obtained by carrying out a process as described above.